Beginning in November 2015, Peru will experience one of the largest El Nio climate events on record. Scientists have historically focused on studying impacts from El Nio in coastal areas due to relatively dry regions experiencing large-scale flooding. Research has largely overlooked the effects of El Nio in the Amazon and its consequences for human health beyond vector-borne disease risk. The Madre de Dios (MDD) region of the Peruvian Amazon is expected to face a challenging El Nio season with over 90% of the population experiencing both excessive drought and flooding. These environmental changes are coupled with an ongoing social challenge: artisanal small-scale gold mining (ASGM) that has rapidly expanded due to construction of the Interoceanic Highway. ASGM releases inorganic mercury (Hg) directly into proximate soil and river sediment, where anaerobic bacteria bio-methylate Hg to form the potent neurotoxicant methylmercury (MeHg) that biomagnifies in the aquatic food web. Communities near and far downstream from ASGM are exposed to high levels of MeHg via consumption of contaminated fish. Our primary hypothesis is that El Nio is associated with increased human MeHg exposure due to elevated rates of Hg bio-methylation in aquatic ecosystems and increased fish consumption. We hypothesize that: (1) El Nio will disrupt agricultural production, leading to increased reliance on fish protein; () Hg released into the environment by ASGM will undergo more rapid bio-methylation due to higher bacterial activity in sediment caused by El Nio- related flooding; (3) fish in flooded rivrs downstream from ASGM and sold in markets will contain higher levels of MeHg; and (4) environmental Hg exposures in adults, children, and developing fetuses will increase with higher dietary exposure and nutritional vulnerability. We will develop a predictive model for human internal MeHg dose that accounts for El Nio-related environmental changes. Our team is uniquely positioned to evaluate the impact of El Nio in the Amazon by leveraging ongoing research in MDD with prior data collected on Hg levels in environmental and human biological samples. In addition, we leverage our long-term collaborative partnerships with community leaders and the Ministry of Health to assist in implementation of our aims. To test our hypotheses, we will collect additional primary data by testing fish, sediment and human biological samples for Hg and other metals in areas and people previously sampled by our team during and following El Nio, conduct monthly food frequency surveys in sentinel households (previously sampled), and initiate a birth cohort (enrolling 10 children per month). Results from this proposed study will help establish whether El Nio flooding is associated with increased MeHg exposure, identify sources of exposures, and determine exposure thresholds associated with observable health effects among persons living in the Amazon. As El Nio events occur regularly and are projected to intensify in the future, this project has significant potential to inform future disaster preparedness and to protect the wellbeing of vulnerable regional populations.